Recent reports suggest that the induction of ornithine decarboxylase (ODC; ED 4.1.1.17) activity may be an obligatory step in the tumor-promotion process. The involvement of adenosine cyclic 3',5'-phosphate (cAMP) and cAMP-dependent protein kinases in the mechanism of activation of ODC has been demonstrated in a number of systems, so this may be a general phenomenon. The objective of the proposed research is to investigate the involvement of cAMP-dependent protein kinases in the induction of ODC activity by tumor-promoting agents. A body of evidence is developing to show that at least two general types of cAMP-dependent protein kinases exit - Type I and Type II - that may fulfill different biological functions. Both the degree of activation and the actual levels of these protein kinases may vary under different conditions of growth or differentiation. In the proposed research, we will examine the effects of a select group of phorbol-type tumor promoters (including some lacking promoting activity) on the amount and degree of activation of both Type I and Type II cAMP-dependent protein kinase. We will then ascertain the degree of correlation between the effects observed and the ability of these agents to induce ODC activity and to promote tumor development.